Stem Cell Transplantation as Immunotherapy for Hematologic Malignancies

Summary

Blood and marrow stem cell transplant has improved the outcome for patients with high-risk hematologic malignancies. However, most patients do not have an appropriate HLA (immune type) matched sibling donor available and/or are unable to identify an acceptable unrelated HLA matched donor through the registries in a timely manner. Another option is haploidentical transplant using a partially matched family member donor.

Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including GVHD and infection due to delayed immune reconstitution. These can, in part, be due to certain white blood cells in the graft called T cells. GVHD happens when the donor T cells recognize the body tissues of the patient (the host) are different and attack these cells. Although too many T cells increase the possibility of GVHD, too few may cause the recipient's immune system to reconstitute slowly or the graft to fail to grow, leaving the patient at high-risk for significant infection.

For these reasons, a primary focus for researchers is to engineer the graft to provide a T cell dose that will reduce the risk for GVHD, yet provide a sufficient number of cells to facilitate immune reconstitution and graft integrity. Building on prior institutional trials, this study will provide patients with a haploidentical graft engineered to specific T cell target values using the CliniMACS system. A reduced intensity, preparative regimen will be used in an effort to reduce regimen-related toxicity and mortality.

Two groups of patients were enrolled on this study. One group included those with high-risk hematologic malignancies and the second group included participants with refractory hematologic malignancies or undergoing a second transplant. The primary aim of the study was to estimate the relapse rate in the one group of research participants with refractory hematologic malignancies or those undergoing second allogeneic transplant. Both groups will be followed and analyzed separately in regards to the secondary objectives.

This study was closed to accrual on April 2006 as it met the specific safety stopping rules regarding occurrence of severe graft vs. host disease. Although this study is no longer open to accrual, the treated participants continue to be followed as directed by the protocol.

Conditions

• Leukemia
• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Chronic Myeloid Leukemia
• Juvenile Myelomonocytic Leukemia
• Myelodysplastic Syndrome
• Paroxysmal Nocturnal Hemoglobinuria
• Hodgkin's Lymphoma
• Non-Hodgkin Lymphoma

Interventions

DRUG

Systematic chemotherapy and antibodies

Systemic chemotherapy and antibodies as follows: Transplant recipients received a reduced intensity conditioning regimen consisting of OKT-3, fludarabine, thiotepa, and melphalan followed by an infusion of a T-cell depleted haploidentical hematopoietic stem cell graft. The antibody Rituximab was administered within 24 hours of the infusion in an effort to prevent PTLPD. In addition to T -cell depletion of the donor product, Mycophenylate mofetil was provided over several months as prophylaxis for GVHD

PROCEDURE

Allogeneic stem cell transplantation

An infusion of HLA mismatched family member donor stem cells processed through the use of the investigational Miltenyi Biotec CliniMACS device

DEVICE

Miltenyi CliniMACS

Miltenyi Biotec CliniMACS stem cell selection device

Sponsors & Collaborators

• St. Jude Children's Research Hospital

  lead OTHER

Principal Investigators

• Gregory Hale, M.D. · St. Jude Children's Research Hospital

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

2 Years

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2005-08-31

Primary Completion

2006-07-31

Completion

2009-01-31

Countries

• United States

Study Locations